Project Summary/Abstract HIV-negative pregnant and breastfeeding women in South Africa are at extremely high risk of HIV acquisition despite increased access to and initiation of antiretroviral therapy (ART) in South Africa. We urgently need effective interventions to reduce HIV incidence in pregnant and breastfeeding women. Currently PrEP is one of the only female controlled methods that is effective for preventing HIV acquisition. PrEP-PP is a study of pre-exposure prophylaxis (PrEP) among HIV-1 seronegative Pregnant and Postpartum women in two South African urban primary health care facilities. Effective use of PrEP could contribute to eliminating maternal HIV acquisition, and hence eliminating mother to child HIV transmission (MTCT). However, PrEP efficacy requires adherence during periods of sexual activity and adherence requires PrEP access, awareness and counseling. Currently, a major obstacle in the field is the lack of knowledge of women's initiation, retention and adherence to PrEP during pregnancy and breastfeeding periods in Africa. Now is the time to evaluate how best to provide PrEP to vulnerable pregnant and breastfeeding women as WHO recently developed guidelines for providing PrEP in pregnancy and breastfeeding women but there are limited data on acceptability, initiation and adherence in pregnant and breastfeeding women in Africa where the burden of HIV is greatest. Our study will focus on the following specific aims: 1. Determine the distribution of women across the PrEP cascade (initiation, retention, and adherence) and outcomes (HIV acquisition, transmission, and adverse events) in a cohort of pregnant and breastfeeding women in Cape Town, South Africa 2. Evaluate patient and provider-level factors associated with the PrEP cascade (initiation, retention and adherence) using quantitative and qualitative approaches 3. Apply an established mathematical model to simulate the impact of improvement in the PrEP cascade on HIV infections averted (maternal and perinatal) Our PrEP-PP study is urgent and essential to understand the PrEP cascade in pregnant and breastfeeding women in South Africa and to identify factors associated with PrEP initiation and adherence to develop interventions to ensure that everyone in this at-risk population can benefit from PrEP. The results from the PrEP-PP study will provide a model for the South African Government, and other Governments in the region, to scale up PrEP delivery among pregnant and breastfeeding women at risk of HIV acquisition and perinatal transmission and contribute to the elimination of perinatal HIV transmission.